Life Sciences Commons^™

Sequestered Sequences: A Bioinformatic Approach To The Forgotten Genome, Dylan Barth

UNLV Theses, Dissertations, Professional Papers, and Capstones

As high throughput sequencing generates ever increasing amounts of genetic and epigenetic data new lines of inquiry open up in the field of genomic research. In this thesis, we discuss three ways in which we can utilize public databases of next generation genomic data in order to study areas of the genome previously ignored by traditional approaches. These include the study of linker regions between domains of proteins, indirect enhancers that do not strongly contact promoters of genes they regulate, and transposon-derived enhancer elements. The work uncovers many exceptions to known biological principles, and adds nuance to our understanding of …

Retrospective Varying Coefficient Association Analysis Of Longitudinal Binary Traits, Gang Xu

UNLV Theses, Dissertations, Professional Papers, and Capstones

Many genetic studies contain rich information on longitudinal phenotypes that require powerful analytical tools for optimal analysis. Genetic analysis of longitudinal data that incorporates temporal variation is important for understanding the genetic architecture and biological variation of complex diseases. Most of the existing methods assume that the contribution of genetic variants is constant over time and fails to capture the dynamic pattern of disease progression. However, the relative influence of genetic variants on complex traits fluctuates over time.We developed several tests to fill the gap of analyzing time-varying genetic effects in longitudinal GWAS for binary traits. First, we propose a …

Strategic Plan For Genomic Competencies Into Undergraduate Nursing Curriculum, Myerann Royce M. Mangalino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Problem: As genomics research continues to grow in medicine and in popular culture, an educational gap in nursing is inevitable. Nurses must have a strong understanding of genetics and genomics to effectively integrate them into current practice.Objectives: The objective is to identify gaps in the current undergraduate curriculum and build threads that may be incorporated into the current curriculum to fill the identified gaps. Methods: The foundation of this project was the Essentials of Genetic and Genomic Nursing: Competencies, Curricula Guidelines, and Outcome Indicators, 2nd Edition (Consensus Panel on Genetic/Genomic Nursing Competencies, 2008). A strategic plan was created to increase …

Improving Self-Efficacy And Knowledge While Reducing Anxiety In High-Risk Breast Cancer Patients Through Standardized Education, Shelley Miles

UNLV Theses, Dissertations, Professional Papers, and Capstones

Breast cancer is the leading cause of death of women in the United States. Patients at high risk for developing cancer are more easily identified in today’s world. Early identification might be due to strong family history or genetic mutations, such as BRCA1 or BRCA2. Screening and risk reduction guidelines have been developed over recent years for these patients. Adherence to these guidelines continues to be a problem. The factors stemming from this problem include lack of knowledge about being high-risk, understanding the guidelines, and anxiety and depression about the perceived risk of developing breast cancer. These factors can cause …

Increasing Genetic Testing Rates To Improve Early Detection And Prevention Of Breast And Ovarian Cancer In Women, Makensey Beth Durrant

UNLV Theses, Dissertations, Professional Papers, and Capstones

Screening rates for cancer related genetic mutations are low in the primary care setting, despite evidence-based guidelines recommending screening in all patients who meet criteria. Genetic mutations, such as the breast cancer susceptibility 1 and 2 (BRCA1/2) gene mutations, drastically increase breast and ovarian cancer risk in patients. The United States Preventive Services Task Force (USPSTF) and the National Comprehensive Cancer Network (NCCN) provide evidence-based guidelines on criteria for genetic testing in women at risk for breast and ovarian cancer related gene mutations. Primary care providers (PCPs), including advanced practice registered nurses (APRNs), are at the front lines of preventative …

Genomic Analysis Of Paenibacillus Larvae Bacteriophages, Casey Stamereilers

UNLV Theses, Dissertations, Professional Papers, and Capstones

American Foulbrood is the most destructive bacterial infection of the honeybee (Apis mellifera) and is caused by the Gram-positive, spore forming bacterium Paenibacillus larvae. Current treatment methods rely on antibiotics, but antibiotics treatments are experiencing a reduction in efficacy due to the recent rise in antibiotic resistant strains of P. larvae. This has been a major catalyst for exploration of alternative treatment methods. Phage therapy is an alternative treatment method that uses viruses that exclusively infect bacteria, known as bacteriophages (phages), to combat bacterial infections. Several experimental studies have shown that phages P. larvae phages are effective at lysing P. …

Bayesian Variable Selection Methods For Genome-Wide Association Studies With Categorical Phenotypes, Benazir Rowe

UNLV Theses, Dissertations, Professional Papers, and Capstones

Genome-wide association studies (GWAS) attempt to find the associations between genetic markers and studied traits (phenotypes). The problem of GWAS is complex and various methods have been developed to approach it. One of such methods is Bayesian variable selection (BVS). We describe the BVS methods in detail and demonstrate the ability of BVS method Posterior Inference via Model Averaging and Subset Selection (piMASS) to improve the power of detecting phenotype-associated genetic loci, potentially leading to new discoveries from existing data without increasing the sample size.

We present several ways to improve and extend the applicability of piMASS for GWAS. The …

Transposable Element Expression In Human Embryo Single-Cell Rna-Seq Data, Corinne Sexton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Transposable elements (TEs) are genetic sequences which are mobile within the genome, including DNA transposons and retrotransposons. Though the vast majority are no longer able to move or duplicate in humans, they still are actively transcribed in both germline and somatic cells, particularly in early human development. TEs are expressed in an extremely cell-type and stage specific pattern during embryogenesis, suggesting that they may either have a regulatory role in the cell or be transcribed along with cell-specific genes. However, earlier studies have focused on hESC models or early embryos up to day 6, with differing patterns of TE expression. …

An Investigation Into Multi-View Error Correcting Output Code Classifiers Applied To Organ Tissue Classification, Daniel Alvarez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Large amounts of data is being generated constantly each day, so much data that it is difficult to find patterns in order to predict outcomes and make decisions for both humans and machines alike. It would be useful if this data could be simplified using machine learning techniques. For example, biological cell identity is dependent on many factors tied to genetic processes. Such factors include proteins, gene transcription, and gene methylation. Each of these factors are highly complex mechanism with immense amounts of data. Simplifying these can then be helpful in finding patterns in them. Error-Correcting Output Codes (ECOC) does …

The Significance Of Mfd And Oxidative Damage In Stationary-Phase Mutagenesis In Bacillus Subtilis, Holly Anne Martin

UNLV Theses, Dissertations, Professional Papers, and Capstones

The process of stationary-phase mutagenesis, also known as adaptative or stress-induced mutagenesis, is a phenomenon where bacterial cells accumulate mutations in non-replicative conditions. This process has mainly been studied in Escherichia coli and Bacillus subtilis; however, the underlying mechanisms found in each of these systems differ. Here, I use B.msubtilis to study previously understudied aspects of stationary-phase mutagenesis. In this dissertation, I describe work that has led to three major discoveries which are described below.

First in B. subtilis, Mfd is important for stationary-phase mutagenesis and its mutagenic function at regions of the genome that are transcriptionally upregulated has been …

Multi-Polygenic Risk Score Prediction Model For Bipolar Disorder, Travis Mize

UNLV Theses, Dissertations, Professional Papers, and Capstones

Bipolar disorder (BP), a severe mental disorder characterized by recurring manic and depressive episodes, has been shown to have a strong genetic underpinning. Current theory suggests that it is the summation of risk alleles, spread across the entirety of the genome, which contributes to the development of BP, as well as other polygenic traits. The comorbid nature of these polygenic traits are often problematic for diagnosticians as the symptomology of the disorders may vary substantially between individuals and can create diagnostic confusion. To alleviate issues such as these, a more objective measure, to be used alongside current diagnostic procedures, is …

Gene Expression Profiling In The Larval Fat Body Of Desiccation Selected Drosophila Melanogaster, Adriana Michelle Charles

UNLV Theses, Dissertations, Professional Papers, and Capstones

Drosophila melanogaster selected for resistance to desiccation (no food or water) display slower development and a higher body mass compared to fed controls due to an extended third larval instar. I hypothesize that desiccation selected D. melanogaster larvae will have a different gene expression profile compared to fed controls. Separate populations of D. melanogaster were subjected to desiccation (no food or water), starvation (no food) until 80-85% mortality, for 75 generations. mRNA from the larval fat body was collected at 88 hours, 96 hours, 112 hours and 120 hours post-hatching. Four replicate samples were used for each condition and time …

The Role Of Mfd In Stationary-Phase Oxidative Damage Repair In Bacillus Subtilis, Katelyn E. Porter

UNLV Theses, Dissertations, Professional Papers, and Capstones

Since the 1950’s it has been shown that bacterial cells accumulate mutations even in non- dividing conditions, but how this type of mutation occurs is still highly debated. In Bacillus subtilis, Mfd, a precursor of the nucleotide excision repair (NER) system, mediates the formation of mutations in stationary-phase or non-replicating cells. In growing cells, Mfd recruits repair when RNA polymerase is stalled during transcription; it then recruits proteins from NER to repair damage. Here, we examine the hypothesis that Mfd mediates the formation of mutations by interacting with cellular components that repair reactive oxygen species (ROS), a natural byproduct of …

Time-Dependent Random Effect Poisson Random Field Model For Polymorphism Within And Between Two Related Species, Shilei Zhou

UNLV Theses, Dissertations, Professional Papers, and Capstones

Molecular evolution is partially driven by mutation, selection, random genetic drift, or combination of the three factors. To quantify the magnitude of these genetic forces, a previously developed time-dependent fixed effect Poisson random field model provides powerful likelihood and Bayesian estimates of mutation rate, selection coefficient, and species divergence time. The assumption of the fixed effect model that selection intensity is constant within a genetic locus but varies across genes is obviously biologically unrealistic, but it serves the original purpose of making statistical inference about selection and divergence between two related species they are individually at mutation-selection-drift inequilibrium. By relaxing …

Sex Determination Using Discriminant Function Analysis In Hispanic Children And Adolescents: A Lateral Cephalometric Study, Alyssa E. Sprowl

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lateral cephalometric radiographs have been used for years to help diagnose skeletal and dental patterns in Orthodontics. Within the last decade, these radiographs have caught the interest of the department of Anthropology for the identification of gender within the adult and adolescent population. Numerous publications have been made but failed to identify sexual dimorphism in the pre-adolescent population. 303 lateral cephalograms of pre and post Latino adolescence age ranging from 6.5 to 17.9 years old were obtained from University of Nevada, Las Vegas (UNLV) digital database. 25 variables were identified and plotted with all linear and angular measurements transferred into …

Relationship Of Global Dna Methylation With Cardiovascular Fitness And Body Composition, Michael Steele Jarrett

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Global DNA Methylation (GDM), an epigenomic modification has been linked to the development of Cardiovascular Disease and its risk factors. Purpose: The purpose of this study was to determine if there is a significant correlation between GDM and cardiovascular fitness, as well as, measures of body composition. Methodology: 26 apparently healthy, adults (11 males) completed a physical activity and diet questionnaire, as well as, had a small blood sample (600μL) collected via finger prick for the determination of GDM. Body composition was assessed by means of a Dual-Energy X-ray Absorptiometry (DEXA) scan, while cardiovascular fitness was evaluated by the …

A Comprehensive Research Framework For Geographic Parthenogenesis In Whiptail Lizards (Genus Aspidoscelis), Adam Leland

UNLV Theses, Dissertations, Professional Papers, and Capstones

One of the most compelling topics in biology has been the ubiquity of sexual reproduction in living organisms. Because the ecological and evolutionary advantages of sex are well founded, those organisms that reproduce asexually remain enigmatic. Parthenogenesis, the clonal reproduction of an all-female species without the need for males, is a relatively common form of asexual reproduction in vertebrates, and has been subject of numerous academic investigations. Many parthenogenic organisms also share aspects of their geographic distributions, such as inhabiting higher latitudes, higher altitudes, islands or island-like habitats, xeric environments, and marginal, disturbed or ecotonal habitats relative to their sexual …

A Genetic, Transgenic, And Transcriptomic Analysis Of Larval Salivary Gland Physiology In Drosophila Melanogaster, Elana A. Paladino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cholesterol is the precursor to a unique class of lipophilic signaling molecules called steroid hormones that initiate the development of sexual characteristics, reactions to stress, and maintenance of metabolism, among many other functions. Although much progress has been made in understanding the function of these signaling hormones, we do not fully understand how a single steroid can cause many distinct, tissue-specific responses. Drosophila melanogaster is an effective model for understanding steroid hormone action because of its simplicity. The steroid molting hormone 20-hydroxyecdysone (hereafter, 20E) is the primary active steroid in Drosophila and mediates not only larval molts and the emergence …

Global And Specific Controls Of Protein Synthesis In Hibernators, Peipei Pan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mammalian hibernation is a highly dynamic physiological process that is composed of a series of torpor bouts, wherein hibernators oscillate between periods of torpor and interbout arousal. Although normally vital to homeostasis, many energetically consumptive processes such as translation or protein synthesis are virtually ceased during hibernation. Earlier studies indicated that protein synthesis had fallen to almost negligible levels. Cap-dependent initiation of translation is well regulated by eukaryotic translation initiation factor 4E (eIF4E) and its binding partner eIF4E-binding protein 1 (4E-BP1) when hibernators cycle in and out the torpor state. Herein, I investigated well-characterized regulatory mechanisms of global and specific …

Molecular Evolution And Historical Biogeography Of New World Birds, Brian T. Smith

UNLV Theses, Dissertations, Professional Papers, and Capstones

Deciphering the patterns of how biodiversity has evolved across time and space has remained a fundamental objective for biologists for the last 200 years. Researchers are faced with the challenge of interpreting the complexity of evolutionary patterns that have been generated over the deep history of the Earth. The advancement of DNA sequencing technology has yielded a new and powerful genetic toolkit that has allowed biologists to address novel evolutionary questions. For my dissertation research, I used molecular genetics and a statistical framework to study the evolution and historical biogeography of birds distributed in North and South America. My dissertation …

Transcriptional Regulation Of Shigella Virulence Plasmid-Encoded Genes By Virb And Crp, Christopher Thomas Hensley

UNLV Theses, Dissertations, Professional Papers, and Capstones

Shigella flexneri is a species of Gram-negative intracellular pathogens that causes bacillary dysentery in humans. Shigella relies on the precise transcriptional regulation of virulence genes, encoded by a large virulence plasmid, for invasion and infection of human colonic epithelial cells. The transcription of most identified virulence genes are regulated through a cascade controlled by the primary regulator of virulence genes, VirF, and the global transcriptional regulator, VirB. Currently, few studies have addressed how individual Shigella virulence genes are precisely regulated for optimal expression during specific stages of pathogenesis and within the constraints of the regulatory cascade. This work addresses how …

Reconstructing Species Responses To Past Climatic Changes Using Niche Modeling And Genetic Data, Tereza Jezkova

UNLV Theses, Dissertations, Professional Papers, and Capstones

Glacial – interglacial cycles have a pronounced impact on species distributions and genetic structure. Many species shift their distributions to lower latitudes and altitudes during the colder glacial periods and expand northwards and up the elevation during warmer interglacial periods. Some species however are capable of adapting to changing environment which allows them to persist in place despite climatic changes. I explored how climatic changes after the last glacial maximum (LGM) effected two species inhabiting the deserts of western North America: one mammal (Chisel-toothed Kangaroo Rat, Dipodomys microps) and one reptile (Desert Horned Lizard, Phrynosoma platyrhinos). I used …

Environmental Influence On Brain, Behavior, And Gene Expression In Drosophila, Xia Wang

UNLV Theses, Dissertations, Professional Papers, and Capstones

Brain development and behavior are sensitive to environmental stimuli. To gain an understanding of how and to what extent environmental variations, particularly with regard to thermal stress and sensory input, affect brain development, function, and genomic activity, in this dissertation, three interrelated studies were conducted in Drosophila melanogaster.

The first study examined the effects of ecologically-relevant hyperthermia stress on development of the Drosophila mushroom body (MB), a conserved sensory integration and associative center in the insect brain. A daily hyperthermic episode throughout larval and pupal development was shown to severely disrupt MB anatomy by reducing intrinsic Kenyon cell neuron …

Transcriptional Regulation Of The Shigella Flexneri Icsp Promoter: Silencing And Anti-Silencing By H-Ns And Virb, Dustin Harrison

UNLV Theses, Dissertations, Professional Papers, and Capstones

Shigella species are gram-negative intracellular pathogens that cause bacillary dysentery in humans. Many genes required for virulence of Shigella are carried on a large 230 kb plasmid and many of these are under the transcriptional control of the histone-like nucleoid structuring protein (H-NS) and by the major virulence regulator VirB. At the non-permissive temperature of 30⁰C, H-NS represses transcription, while at 37⁰C VirB alleviates this repression. This mechanism of gene regulation has been coined "silencing/anti-silencing" and is commonly found in many important bacterial pathogens including Salmonella spp. and Yersinia spp. The icsP gene, encoded by the Shigella virulence plasmid, is …

The Larval Salivary Gland Of Drosophila Melangogaster: A Model System For Temporal And Spatial Steroid Hormone Regulation, Benjamin Constantino

UNLV Theses, Dissertations, Professional Papers, and Capstones

Drosophila melanogaster provides an ideal model organism to test genetic and molecular biological mechanisms within the context of a living animal. For over one hundred years Drosophila continues to produce a boundless extent of informative and important scientific data providing crucial insight into development, disease progression and genetic interactions. A century as a model organism allowed for the development of an abundance of unique genetic and molecular tools allowing researchers to tease apart cellular mechanisms with very little limitation. From the whole adult body to tissue function to molecular networks, if a biological question arises it most likely can be …

The Role Of Ecdysone Signaling In Fat-Body Tissue Remodeling And Pupal Metabolism, Nichole Dinell Bond

UNLV Theses, Dissertations, Professional Papers, and Capstones

Holometabolous insects undergo an astonishing transition during their development. During metamorphosis, the larva dramatically changes form and becomes an adult fly. During this process obsolete larval tissues must be eliminated, while tissues required for further development are retained and often remodeled to meet the needs of the adult fly. Tissue remodeling is characterized by morphological changes of the cells in a tissue mass. In many cases, remodeling is characterized by dissociation of the tissue mass, releasing cells to move freely around the body cavity. This process is also common in wound healing and is a key feature of human disease …

The Role Of Transcription In Stationary Phase Mutagenesis In Bacillus Subtilis, Holly Anne Martin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Stationary phase mutagenesis, also known as stress-induced or adaptive mutagenesis, is defined as the accumulation of mutations during conditions of no net growth or conditions of stress. This process has been implicated in acquiring antibiotic resistance and evasion of host immune responses in microbial pathogens and in the generation of mutations that lead to neoplasia in animal cells. Previous work has shown that defects in DNA synthesis and repair systems contribute to the formation of adaptive mutations; however the role of transcription in the accumulation of mutations is still being examined. It is speculated that transcriptional derepression leads to an …

When Did The Ancestors Of Polynesia Begin To Migrate To Polynesia? The Mtdna Evidence, David Lesniewski

UNLV Theses, Dissertations, Professional Papers, and Capstones

The timing and nature of the migration of the ancestors of the Polynesian people is debated by two competing theories. The "Express Train" and "Slow Boat" theories assert that the migration of the Proto-Polynesian people began around 6,000 years before present (BP) or around 10,000 years BP respectively. Through the use of haplogroups and specific genetic mutations a direct relationship between the Proto-Polynesians and modern Polynesians was attempted to test which of these theories was correct. The ancient skeletal remains from the island of Borneo currently housed at UNLV were used in this study as their dates fall within both …